|
Principal Investigator: Dr. Bettina Wagner
Contact Information: E-mail: bw75@cornell.edu - Phone: 607-255-5660
Sponsor: Harry M. Zweig Memorial Fund for Equine Research
Grant Number: N/A
Title: IgE and IgG(T) Antibodies in Allergy of the Horse
Annual Direct Cost: $41,495
Project Period: 01/01/06-12/31/07
Description (provided by applicant): Type I hypersensitivities, or allergies, are mediated by immunoglobulin E (IgE) that causes the release of inflammatory substances from mast cells. During the initial 8 months of this project, we provided the first formal evidence that IgE mediates allergy in the horse by performing a classical Prausnitz-Kttstner experiment. In addition, we discovered that immediate skin reactions can be reproducibly induced in horses by injection of monoclonal antibodies to IgE alone. We also found that one of the control anti-IgG antibodies (anti-IgG(T)) induced a similar reaction, while other anti-IgG antibodies were negative in this test. The finding that IgG(T) can mediate an immediate skin reaction in the horse was unexpected and is novel. We have previously shown that young horses do not produce IgE for the first year of life. IgG(T) production is known to begin by 8 weeks of age. In horses, clinical manifestation of allergy often occurs at 4-5 years of age, while sensitization to allergen can precede clinical signs by several years. These observations lead to our hypothesis that type I allergies in horses can be mediated by IgG(T) as well as IgE and that IgG(T) is the early antibody influencing the manifestation of an allergic response, The goal of this proposal is to test whether IgE and IgG(T) both contribute to clinical allergy in the horse and to characterize their specific roles in disease. This would be investigated by two aims within the two-year funding period of the project:
Aim 1 is to test if IgG(T) can mediate a Prausnitz-Ktistner reaction in vivo through passive transfer of purified IgG(T) from allergic horses to normal recipients, followed by intradermal injection of allergen. In addition, the skin reactions induced by IgG(T) and IgE will be compared in this aim. Biopsies would be taken form the reactive sides in the skin and would be investigated by immunohistochemistry and RT-PCR.
Aim 2 will test whether mast cells of young horses which do not have IgE antibodies are sensitized to allergen by IgG(T) antibodies, in the absense of IgE the influence of IgG(T) on the development of allergy can be measured. We would performed skin testing with allergens, injection of anti-IgG(T) and anti-IgE antibodies in vivo and cellular degranulation assays in vitro. Horses between 6 months to 3 years of age would be tested. Aim2 will also test at which age sensitization with IgE reactivity to allergens is detectable. This project would provide new knowledge about the early induction of allergy in horses that can be applied to allergy treatments and preventive strategies to avoid the manifestation of clinical hypersensitivity.
| 
